• 1.山東大學(xué)第二醫(yī)院肛腸外科(山東濟(jì)南 250033);;
  • 2.山東中醫(yī)藥大學(xué)微循環(huán)實(shí)驗(yàn)室(山東濟(jì)南 250014);

目的  探討zeste基因增強(qiáng)子同源物2(EZH2) mRNA在結(jié)直腸癌組織中的表達(dá)及其與結(jié)直腸癌臨床病理特征的關(guān)系。
方法  采用PCR方法檢測(cè)了27例結(jié)直腸癌患者的癌組織、癌旁組織和正常黏膜上皮組織中EZH2mRNA的表達(dá)情況,并分析其與結(jié)直腸癌臨床病理特征的關(guān)系。
結(jié)果  結(jié)直腸癌組織、癌旁組織及正常黏膜上皮組織中EZH2mRNA的表達(dá)水平分別為3.01±1.29、1.20±0.69及0.87±0.37,其在結(jié)直腸癌組織的表達(dá)水平最高(P<0.01),而在癌旁組織和正常黏膜上皮組織中的表達(dá)差異無(wú)統(tǒng)計(jì)學(xué)意義(P=0.403)。結(jié)直腸癌組織中EZH2mRNA的表達(dá)與其TNM分期(P=0.002)和組織分化程度(P=0.005)均有關(guān),與年齡(P=0.388)、性別(P=0.963)、腫瘤直徑(P=0.579)、組織學(xué)類型(P=0.945)、腫瘤位置(P=0.611)及淋巴結(jié)轉(zhuǎn)移(P=0.449)均無(wú)關(guān)。
結(jié)論  EZH2mRNA在結(jié)直腸癌組織中呈高表達(dá),可能在結(jié)直腸癌的發(fā)生和發(fā)展過(guò)程中起關(guān)鍵作用,可作為判斷結(jié)直腸癌惡性程度及進(jìn)程的參考指標(biāo)之一。

引用本文: 呂艷鋒,韓冰冰,禹化龍,王建新. EZH2 mRNA在結(jié)直腸癌組織中的表達(dá)及其臨床意義△. 中國(guó)普外基礎(chǔ)與臨床雜志, 2013, 20(7): 752-755. doi: 復(fù)制

1. Varambally S, Dhanasekaran SM, Zhou M, et al. The polycomb group protein EZH2 is involved in progression of prostate cancer[J]. Nature, 2002, 419(6907):624-629.
2. Bracken AP, Pasini D, Capra M, et al. EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer[J]. EMBO J, 2003, 22(20):5323-5335.
3. Hanson RD, Hess JL, Yu BD, et al. Mammalian trithorax and polycomb-group homologues are antagonistic regulators of homeoticdevelopment[J]. Proc Natl Acad Sci U S A, 1999, 96(25):14372-14377.
4. Jacobs JJ, van Lohuizen M. Polycomb repression:from cellularmemory to cellular proliferation and cancer[J]. Biochim BiophysActa, 2002, 1602(2):151-161.
5. Cao R, Wang L, Wang H, et al. Role of histone H3 lysine 27 methylation in polycomb-group silencing[J]. Science, 2002, 298(5595):1039-1043.
6. Kuzmichev A, Jenuwein T, Tempst P, et al. Different EZH2-containing complexes target methylation of histone H1 or nucleosomal histone H3[J]. Mol Cell, 2004, 14(2):183-193.
7. Simon JA, Lange CA. Roles of the EZH2 histone methyltransferase in cancer epigenetics[J]. Mutat Res, 2008, 647(1-2):21-29.
8. Bachmann IM, Halvorsen OJ, Collett K, et al. EZH2 expression is associated with high proliferation rate and aggressive tumor subg-roups in cutaneous melanoma and cancers of the endometrium,prostate, and breast[J]. J Clin Oncol, 2006, 24(2):268-273.
9. Kozakowski N, Soleiman A, Pammer J. BMI-1 expression is inversely correlated with the grading of renal clear cell carcinoma[J]. Pathol Oncol Res, 2008, 14(1):9-13.
10. Croonquist PA, Van Ness B. The polycomb group protein enhancerof zeste homolog 2 (EZH2) is an oncogene that influences myelomacell growth and the mutant ras phenotype[J]. Oncogene, 2005, 24(41):6269-6280.
11. Breuer RH, Snijders PJ, Smit EF, et al. Increased expression of the EZH2 polycomb group gene in BMI-1-positive neoplastic cells during bronchial carcinogenesis[J]. Neoplasia, 2004, 6(6):736-743.
12. Weikert S, Christoph F, Köllermann J, et al. Expression levels of the EZH2 polycomb transcriptional repressor correlate with aggressiveness and invasive potential of bladder carcinomas[J]. Int J Mol Med, 2005, 16(2):349-353.
13. Arisan S, Buyuktuncer ED, Palavan-Unsal N, et al. Increased expression of EZH2, a polycomb group protein, in bladder carcinoma[J]. Urol Int, 2005, 75(3):252-257.
14. Cardoso C, Mignon C, Hetet G, et al. The human EZH2 gene:genomic organisation and revised mapping in 7q35 within the critical region for malignant myeloid disorders[J]. Eur J Hum Genet, 2000, 8(3):174-180.
15. Tonini T, Bagella L, D’andrilli G, et al. Ezh2 reduces the abilityof HDAC1-dependent pRb2/p130 transcriptional repression of cyclin A[J]. Oncogene, 2004, 23(28):4930-4937.
16. Sewalt RG, van der Vlag J, Gunster MJ, et al. Characterization of interactions between the mammalian polycomb-group proteins Enx1/EZH2 and EED suggests the existence of different mammalian polycomb-group protein complexes[J]. Mol Cell Biol, 1998, 18(6):3586-3595.
17. Collett K, Eide GE, Arnes J, et al. Expression of enhancer of zeste homologue 2 is significantly associated with increased tumor cell proliferation and is a marker of aggressive breast cancer[J]. Clin Cancer Res, 2006, 12(4):1168-1174.
18. Choi JH, Song YS, Yoon JS, et al. Enhancer of zeste homolog 2 expression is associated with tumor cell proliferation and metastasisin gastric cancer[J]. APMIS, 2010, 118(3):196-202.
19. Matsukawa Y, Semba S, Kato H, et al. Expression of the enha-ncer of zeste homolog 2 is correlated with poor prognosis in humangastric cancer[J]. Cancer Sci, 2006, 97(6):484-491.
20. Su IH, Basavaraj A, Krutchinsky AN, et al. Ezh2 controls B cell development through histone H3 methylation and Igh rearrangement[J]. Nat Immunol, 2003, 4(2):124-131.
21. Kleer CG, Cao Q, Varambally S, et al. EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells[J]. Proc Natl Acad Sci U S A, 2003, 100(20):11606-11611.
22. Raaphorst FM, Meijer CJ, Fieret E, et al. Poorly differentiated breast carcinoma is associated with increased expression of the human polycomb group EZH2 gene[J]. Neoplasia, 2003, 5(6):481-488.
23. Zetter BR, Banyard J. Cancer. The silence of the genes[J]. Nature, 2002, 419(6907):572-573.
24. Sun BH, Zhang J, Wang BJ, et al. Analysis of in vivo patterns of caspase 3 gene expression in primary hepatocellular carcinoma and its relationship to p21(WAF1) expression and hepatic apoptosis[J]. World J Gastroenterol, 2000, 6(3):356-360.
25. Sudo T, Utsunomiya T, Mimori K, et al. Clinicopathological significance of EZH2 mRNA expression in patients with hepatocellular carcinoma[J]. Br J Cancer, 2005, 92(9):1754-1758.
  1. 1. Varambally S, Dhanasekaran SM, Zhou M, et al. The polycomb group protein EZH2 is involved in progression of prostate cancer[J]. Nature, 2002, 419(6907):624-629.
  2. 2. Bracken AP, Pasini D, Capra M, et al. EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer[J]. EMBO J, 2003, 22(20):5323-5335.
  3. 3. Hanson RD, Hess JL, Yu BD, et al. Mammalian trithorax and polycomb-group homologues are antagonistic regulators of homeoticdevelopment[J]. Proc Natl Acad Sci U S A, 1999, 96(25):14372-14377.
  4. 4. Jacobs JJ, van Lohuizen M. Polycomb repression:from cellularmemory to cellular proliferation and cancer[J]. Biochim BiophysActa, 2002, 1602(2):151-161.
  5. 5. Cao R, Wang L, Wang H, et al. Role of histone H3 lysine 27 methylation in polycomb-group silencing[J]. Science, 2002, 298(5595):1039-1043.
  6. 6. Kuzmichev A, Jenuwein T, Tempst P, et al. Different EZH2-containing complexes target methylation of histone H1 or nucleosomal histone H3[J]. Mol Cell, 2004, 14(2):183-193.
  7. 7. Simon JA, Lange CA. Roles of the EZH2 histone methyltransferase in cancer epigenetics[J]. Mutat Res, 2008, 647(1-2):21-29.
  8. 8. Bachmann IM, Halvorsen OJ, Collett K, et al. EZH2 expression is associated with high proliferation rate and aggressive tumor subg-roups in cutaneous melanoma and cancers of the endometrium,prostate, and breast[J]. J Clin Oncol, 2006, 24(2):268-273.
  9. 9. Kozakowski N, Soleiman A, Pammer J. BMI-1 expression is inversely correlated with the grading of renal clear cell carcinoma[J]. Pathol Oncol Res, 2008, 14(1):9-13.
  10. 10. Croonquist PA, Van Ness B. The polycomb group protein enhancerof zeste homolog 2 (EZH2) is an oncogene that influences myelomacell growth and the mutant ras phenotype[J]. Oncogene, 2005, 24(41):6269-6280.
  11. 11. Breuer RH, Snijders PJ, Smit EF, et al. Increased expression of the EZH2 polycomb group gene in BMI-1-positive neoplastic cells during bronchial carcinogenesis[J]. Neoplasia, 2004, 6(6):736-743.
  12. 12. Weikert S, Christoph F, Köllermann J, et al. Expression levels of the EZH2 polycomb transcriptional repressor correlate with aggressiveness and invasive potential of bladder carcinomas[J]. Int J Mol Med, 2005, 16(2):349-353.
  13. 13. Arisan S, Buyuktuncer ED, Palavan-Unsal N, et al. Increased expression of EZH2, a polycomb group protein, in bladder carcinoma[J]. Urol Int, 2005, 75(3):252-257.
  14. 14. Cardoso C, Mignon C, Hetet G, et al. The human EZH2 gene:genomic organisation and revised mapping in 7q35 within the critical region for malignant myeloid disorders[J]. Eur J Hum Genet, 2000, 8(3):174-180.
  15. 15. Tonini T, Bagella L, D’andrilli G, et al. Ezh2 reduces the abilityof HDAC1-dependent pRb2/p130 transcriptional repression of cyclin A[J]. Oncogene, 2004, 23(28):4930-4937.
  16. 16. Sewalt RG, van der Vlag J, Gunster MJ, et al. Characterization of interactions between the mammalian polycomb-group proteins Enx1/EZH2 and EED suggests the existence of different mammalian polycomb-group protein complexes[J]. Mol Cell Biol, 1998, 18(6):3586-3595.
  17. 17. Collett K, Eide GE, Arnes J, et al. Expression of enhancer of zeste homologue 2 is significantly associated with increased tumor cell proliferation and is a marker of aggressive breast cancer[J]. Clin Cancer Res, 2006, 12(4):1168-1174.
  18. 18. Choi JH, Song YS, Yoon JS, et al. Enhancer of zeste homolog 2 expression is associated with tumor cell proliferation and metastasisin gastric cancer[J]. APMIS, 2010, 118(3):196-202.
  19. 19. Matsukawa Y, Semba S, Kato H, et al. Expression of the enha-ncer of zeste homolog 2 is correlated with poor prognosis in humangastric cancer[J]. Cancer Sci, 2006, 97(6):484-491.
  20. 20. Su IH, Basavaraj A, Krutchinsky AN, et al. Ezh2 controls B cell development through histone H3 methylation and Igh rearrangement[J]. Nat Immunol, 2003, 4(2):124-131.
  21. 21. Kleer CG, Cao Q, Varambally S, et al. EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells[J]. Proc Natl Acad Sci U S A, 2003, 100(20):11606-11611.
  22. 22. Raaphorst FM, Meijer CJ, Fieret E, et al. Poorly differentiated breast carcinoma is associated with increased expression of the human polycomb group EZH2 gene[J]. Neoplasia, 2003, 5(6):481-488.
  23. 23. Zetter BR, Banyard J. Cancer. The silence of the genes[J]. Nature, 2002, 419(6907):572-573.
  24. 24. Sun BH, Zhang J, Wang BJ, et al. Analysis of in vivo patterns of caspase 3 gene expression in primary hepatocellular carcinoma and its relationship to p21(WAF1) expression and hepatic apoptosis[J]. World J Gastroenterol, 2000, 6(3):356-360.
  25. 25. Sudo T, Utsunomiya T, Mimori K, et al. Clinicopathological significance of EZH2 mRNA expression in patients with hepatocellular carcinoma[J]. Br J Cancer, 2005, 92(9):1754-1758.